The hydronaphthalene structure can be found in many natural products and pharmaceutical agents. These include homochelidonine (structure I below; Slavik, J.; et al., Collect. Czech. Chem. Commun. 30:3697 (1965); Spath, E., et al., Ber., 64:1123 (1931); Bersch, H. W., Arch. Pharm. (Weinheim, Ger.), 2914:91 (1958)) an alkaloid isolated from Chelidonium plants, dihydrexidine (structure 2 below; Snyder, S. E., J. Med. Chem., 38:2395 (1995)) which shows antiparkinsonian character, etoposide (structure 3 below; Kamal, A., et al., Tetrahedron Lett. 37:3359 (1996)) which is used in the treatment of various cancers, and SF-2315B (structure 4 below; Kim, K., et al., J. Org. Chem. 60:6866 (1995)) which is a viral reverse transcriptase inhibitor. In addition., CNS agents, immunoregulatory agents and antibiotics contain variations on this framework (Perrone. R., et al., J. Med. Chem. 38:942 (1995)).

Given the large number of pharmaceutically useful compounds which contain this core skeleton, new methodology which produces functionalized hydronaphthalene skeletons (structure 1) would clearly be of value.

Previous work on oxabicyclic ring opening reactions led to a catalytic enantioselective route to dihydronaphthol (Lautens, M., et al., Tetrahedron 54:1107 (1998)) which was a key step in the total synthesis of sertraline (Lautens, M., et al., J. Org. Chem. 63:5276 (1997)). However, little is known about the ring opening of oxabenzonorbornadiene or similar compounds with the incorporation of nucleophiles during the ring opening step. Duan and Chen developed a method of introducing aryl groups by using catalytic amounts of palladium (Duan, J.-P., et al., Tetrahedron Lett., 34:4019 (1993); Duan, J.-P., et al., Organometallics 14:1608 (1995)). Moinet et al., later developed an enantioselective version of this reaction but the yields were low (Tetrahedron Lett., 36:2051 (1995)).
Catalytic organometallic processes that form carbon-heteroatom bonds are far fewer in number than those which form carbon-carbon bonds. The Wacker Process (Henry, P. M., Paladium Catalysed Oxidation of Hydrocarbons, vol. 2, Reidel, Boston, (1980)), oxidative carbonylations of amines and alcohols (Applied Homogeneous Catalysis with Oranometallic Compounds: A Comprehensive Handbook in Two Volumes (eds.: B. Cornils, W. A. Herrmann), VCH, New York, (1984)) and the formation of arylamines and aryl ethers (Hartwig, J. F., Agnew. Chem. Int. Ed. 37:2046 (1998); Widenhoefer, R. A., et al., J. Am. Chem. Soc. 119:6787 (1997)) are a few that have been described to date.